title: Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease: a randomized placebo-controlled trial.
abstract: BACKGROUND
  Endogenous opioid peptides have been shown to play a role in the development and/or perpetuation of inflammation. We hypothesize that the endogenous opioid system is involved in inflammatory bowel disease, and antagonism of the opioid-opioid receptor will lead to reversal of inflammation.
  
  
  OBJECTIVE
  A randomized double-blind placebo-controlled study was designed to test the efficacy and safety of an opioid antagonist for 12 weeks in adults with active Crohn's disease.
  
  
  METHODS
  Forty subjects with active Crohn's disease were enrolled in the study. Randomized patients received daily oral administration of 4.5-mg naltrexone or placebo. Providers and patients were masked to treatment assignment. The primary outcome was the proportion of subjects in each arm with a 70-point decline in Crohn's Disease Activity Index score (CDAI). The secondary outcome included mucosal healing based upon colonoscopy appearance and histology.
  
  
  RESULTS
  Eighty-eight percent of those treated with naltrexone had at least a 70-point decline in CDAI scores compared to 40% of placebo-treated patients (p = 0.009). After 12 weeks, 78% of subjects treated with naltrexone exhibited an endoscopic response as indicated by a 5-point decline in the Crohn's disease endoscopy index severity score (CDEIS) from baseline compared to 28% response in placebo-treated controls (p = 0.008), and 33% achieved remission with a CDEIS score <6, whereas only 8% of those on placebo showed the same change. Fatigue was the only side effect reported that was significantly greater in subjects receiving placebo.
  
  
  CONCLUSIONS
  Naltrexone improves clinical and inflammatory activity of subjects with moderate to severe Crohn's disease compared to placebo-treated controls. Strategies to alter the endogenous opioid system provide promise for the treatment of Crohn's disease.
authors.affiliation: Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, Hershey, PA 17033, USA. jsmith2@psu.edu
authors.forename: Jill P
authors.initials: JP
authors.lastname: Smith
authors.forename: Sandra I
authors.initials: SI
authors.lastname: Bingaman
authors.forename: Francesca
authors.initials: F
authors.lastname: Ruggiero
authors.forename: David T
authors.initials: DT
authors.lastname: Mauger
authors.forename: Aparna
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Christopher O
authors.initials: CO
authors.lastname: McGovern
authors.forename: Ian S
authors.initials: IS
authors.lastname: Zagon
mesh_terms: D000328:Adult; D000368:Aged; D003113:Colonoscopy; D003424:Crohn Disease / Q000188:drug therapy*; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone